The Program Project Grant (PPG) continues to be focused on the plasticity of neural and muscular tissue with the plasticity being studied from the regulation of gene expression to locomotion. The principal objectives are to understand the mechanism of neuromuscular plasticity in response to spinal cord injury (SCI). The PPG strategies incorporate models of SCI with the use of mice, rats and humans. Project I will focus on the role neural activity-dependent and neural activity-independent factors play in the control of genes that express muscle proteins. The molecular events that control muscle atrophy and how these genes respond to specific electro-mechanical stimulation patterns will be determined. A novel approach to our studies of locomotion in Projects II-V is the use of newly developed robotic technology to quantify and control locomotion. In Project II we will determine whether the spinal cord uses a modular strategy to generate a kinematically correct step cycle, even when the step cycle is mechanically perturbed. In addition, initial efforts will be made to localize the neural populations that execute the necessary corrective responses to the perturbation and to determine if the learning-related events utilize similar biochemical strategies to those found for learning in the hippocampus. Project III is focused on defining the ultrastructural synaptic reorganization around flexor and extensor motoneurons following SCI and step training. Project IV is designed to identify the effects of the loss of selected descending and ascending spinal pathways on locomotor performance, how step training will modulate this effect and the role of astrocytes in mediating those effects. In Project V, we will study neuromotor control properties to motor task specific training in humans with a complete SCI. These projects will be supported by three Cores: an Administrative (Core A), Animal (Core B) and Data Processing (Core C) Core.